Wearable, noninvasive glucose sensing methods and systems

Abstract

New wearable systems for noninvasive glucose sensing include an ultrasound generator, an ultrasound detector and a feedback unit. Methods for noninvasive glucose sensing using a wearable device include measuring a thickness (geometrical and/or optical) of a target tissue or a time of flight of ultrasound or optical pulses in the target tissue and determining a glucose value from the thickness of the target tissue or the time of flight in the target tissue in accordance with a target tissue thickness (geometrical and/or optical) or time of flight versus glucose calibration curve.

I claim: 
     
       1. A wearable apparatus for glucose sensing comprising:
 (a) a noninvasive glucose sensor, adapted to be in contact with or attached to a target tissue, comprising:
 (i) an ultrasound generator configured to direct ultrasound pulses or waves into the target tissue, and 
 (ii) an ultrasound detector configured to:
 (1) detect ultrasound pulses or waves reflected from the target tissue using reflection, focused reflection, refraction, scattering, polarization, transmission, confocal, interferometric, low-coherence, and/or a low-coherence interferometry technique, and 
 (2) generate a signal corresponding to the detected ultrasound pulses or waves, 
 
 
 (b) a processor configured to:
 (i) receive the signal from the ultrasound detector, 
 (ii) measure:
 (1) at least one time of flight of the ultrasound pulses or waves reflected from or transmitted through the target tissue evidencing boundaries or interfaces within the target tissue, and/or 
 (2) at least one dimension of the target tissue evidencing a specific tissue layer within the target tissue, wherein the dimension includes thickness, length, width, diameter, curvature, or roughness; and 
 
 (iii) determine a glucose concentration value from:
 (1) the at least one measured time of flight, and/or 
 (2) the at least one measured dimension, and 
 
 
 (c) a feedback unit including a display and configured to display a current glucose value or a plot of glucose values versus time, 
 wherein the target tissue is associated with an arm, a forearm, a wrist, a shoulder, a hand, a palm, a finger, an abdomen, a chest, a neck, a head, an ear, an eye, a back, a leg, a foot, or mixtures and combinations thereof, and 
 wherein target tissue comprises a skin tissue, an eye tissue, a mucosal tissue, a nail bed, a lunula, a connective tissue, a muscle tissue, a blood vessel, a cartilage tissue, a tendon tissue, or mixtures and combinations thereof. 
 
     
     
       2. The apparatus of  claim 1 , wherein the ultrasound pulses or waves have a frequency range from about 20 kHz to about 10 Gigahertz, the ultrasound pulses or waves comprise two or multiple frequencies within the frequency range or a broad-band of frequencies within the frequency range. 
     
     
       3. The apparatus of  claim 1 , wherein the ultrasound generator comprises: (1) a piezoelectric element adapted to direct ultrasound pulses or waves into the target tissue, (2) a light source adapted to direct optical pulses into the target tissue to generate thermoelastic ultrasound pulses or waves within the target tissue, (3) a light source adapted to direct optical pulses into an optically absorbing medium to generate ultrasound pulses or waves directed into the target tissue, or (4) a radiofrequency source adapted to direct radiofrequency pulses into a radiofrequency absorbing medium to generate ultrasound pulses or waves directed into the target tissue and wherein all of the pulses are in the range from about 1 femtosecond to about 1 microsecond. 
     
     
       4. The apparatus of  claim 1 , wherein:
 the glucose sensor, the processor, and the feedback unit are integral to form an integral apparatus, or 
 the glucose sensor is separate from the processor and feedback unit to form a separated apparatus, wherein the sensor is configured to transmit the signal to the processor. 
 
     
     
       5. The apparatus of  claim 4 , wherein:
 the integral apparatus comprises:
 a wrist watch further comprising an invasive glucose sensor configured to use blood or interstitial fluid to calibrate the noninvasive glucose sensor, or 
 a pair of glasses, wherein the feedback unit is a head up display associated with the glasses, or 
 
 the separated apparatus comprises a contact lens including the noninvasive glucose sensor. 
 
     
     
       6. The apparatus of  claim 5 , wherein the wrist watch further comprises of a pulse rate monitor, a blood oxygenation monitor, a body temperature monitor, and/or a blood pressure monitor. 
     
     
       7. The apparatus of  claim 6 , wherein the monitors of pulse rate, blood oxygenation, body temperature, and/or blood pressure wirelessly communicate with a cell phone which displays current glucose concentration and a graph of glucose concentration vs. time. 
     
     
       8. The apparatus of  claim 7 , wherein the monitors or cell phone communicate wirelessly with a health care facility or a non-health care facility. 
     
     
       9. The apparatus of  claim 1 , further comprising:
 (d) an insulin patch or an insulin pump under control of the processor. 
 
     
     
       10. The apparatus of  claim 1 , wherein the processor is further configured to transmit the current glucose concentration and/or the graph to medical personnel. 
     
     
       11. The apparatus of  claim 1 , wherein the glucose concentration value is determined from:
 (a) the at least one ultrasound time of flight in accordance with an ultrasound time of flight versus glucose calibration curve, and 
 (b) the at least one ultrasound dimension in accordance with an ultrasound dimension versus glucose calibration curve. 
 
     
     
       12. A method for noninvasive glucose sensing comprising the steps of:
 generating ultrasound pulses or waves using a wearable apparatus comprising:
 (a) a noninvasive glucose sensor, adapted to be in contact with or attached to a target tissue, comprising:
 (i) an ultrasound generator configured to direct ultrasound pulses or waves into the target tissue, and 
 (ii) an ultrasound detector configured to:
 (1) detect ultrasound pulses or waves reflected from the target tissue using reflection, focused reflection, refraction, scattering, polarization, transmission, confocal, interferometric, low-coherence, and/or a low-coherence interferometry technique, and 
 (2) generate a signal corresponding to the detected ultrasound pulses or waves, 
 
 
 (b) a processor configured to:
 (i) receive the signal from the ultrasound detector and measure:
 (1) at least one time of flight of the ultrasound pulses or waves reflected from or transmitted through the target tissue evidencing boundaries or interfaces within the target tissue, and/or 
 (2) at least one dimension of the target tissue evidencing a specific tissue layer within the target tissue, wherein the dimension includes thickness, length, width, diameter, curvature, or roughness, and 
 
 (ii) determine a glucose concentration value from:
 (1) the at least one measured time of flight, and/or 
 (2) the at least one measured dimension, and 
 
 
 (c) a feedback unit including a display and configured to display a current glucose value or a plot of glucose values versus time, 
 
 directing the ultrasound pulses or waves into the target tissue; 
 detecting:
 (a) reflected, refracted, scattered, back-scattered, or forward-scattered ultrasound pulses or waves from the target tissue using the ultrasound detector, and/or 
 (b) transmitted ultrasound pulses or waves passing through target tissue using the ultrasound detector; 
 
 measuring:
 (a) at least one ultrasound time of flight based on the detected ultrasound pulses or waves evidencing boundaries or interfaces within the target tissue or passing through the target tissue based on changes in the ultrasound pulses or waves at the boundaries or interfaces using a processor, and/or 
 (b) at least one ultrasound dimension of a specific tissue layer within the target tissue including a thickness, length, width, diameter, curvature, or roughness based on the detected ultrasound pulses or waves using the processor; and 
 
 determining a glucose concentration value from:
 (a) the at least one ultrasound time of flight in, and/or 
 (b) the at least one ultrasound dimension, 
 
 wherein the target tissue is associated with an arm, a forearm, a wrist, a shoulder, a hand, a palm, a finger, an abdomen, a chest, a neck, a head, an ear, an eye, a back, a leg, a foot, or mixtures and combinations thereof. 
 
     
     
       13. The method of  claim 12 , wherein:
 the measuring step comprises measuring:
 (a) the at least one ultrasound time of flight based on the detected ultrasound pulses or waves evidencing the boundaries or interfaces within the target tissue using the processor, and 
 (b) the at least one ultrasound dimension of the specific tissue layer within the target tissue based on the detected ultrasound pulses or waves using the processor, where the ultrasound dimension includes thickness, length, width, diameter, curvature, or roughness, and 
 
 the determining step comprises determining a glucose concentration value from:
 (a) the at least one ultrasound time of flight in accordance with an ultrasound time of flight versus glucose calibration curve, and 
 (b) the at least one ultrasound dimension in accordance with an ultrasound dimension versus glucose calibration curve. 
 
 
     
     
       14. The method of  claim 12 , further comprising:
 measuring an attenuation, a phase, and a frequency spectrum of the detected ultrasound pulses or waves to improve an accuracy and specificity of the glucose concentration value. 
 
     
     
       15. The method of  claim 12 , wherein, in the generating, directing, detecting, measuring, and determining steps, the target tissue comprises a skin tissue, an eye tissue, a mucosal tissue, a nail bed, a lunula, a connective tissue, a muscle tissue, a blood vessel, a cartilage tissue, or a tendon tissue and wherein the skin tissue includes a dermis, an epidermis, or subcutaneous fat and the eye tissue includes a lens, an anterior chamber, a vitreous cavity, an eye ball, or a sclera. 
     
     
       16. The method of  claim 12 , wherein, in the generating, directing, detecting, measuring, and determining steps, the ultrasound pulses or waves have a frequency range from about 20 kHz to about 10 Gigahertz, the ultrasound pulses or waves comprise two or multiple frequencies within the frequency range or a broad-band of frequencies within the frequency range. 
     
     
       17. The method of  claim 12 , wherein, in the generating step, the ultrasound generator comprises: (1) a piezoelectric element adapted to direct ultrasound pulses or waves into the target tissue, (2) a light source adapted to direct optical pulses into the target tissue to generate thermoelastic ultrasound pulses or waves within the target tissue, (3) a light source adapted to direct optical pulses into an optically absorbing medium to generate ultrasound pulses or waves directed into the target tissue, or (4) a radiofrequency source adapted to direct radiofrequency pulses into a radiofrequency absorbing medium to generate ultrasound pulses or waves directed into the target tissue and wherein all of the pulses are in the range from about 1 femtosecond to about 1 microsecond. 
     
     
       18. The method of  claim 12 , further comprising:
 supplying insulin to the target tissue via:
 (d) an insulin patch or an insulin pump under control of the processor. 
 
 
     
     
       19. The method of  claim 12 , further comprising:
 transmitting via the processor the current glucose concentration and/or the graph to medical personnel. 
 
     
     
       20. The method of  claim 12 , wherein, in the generating, directing, detecting, measuring, and determining steps:
 the glucose sensor, the processor, and the feedback unit are integral to form an integral apparatus, or 
 the glucose sensor is separate from the processor and feedback unit to form a separated apparatus, wherein the sensor is configured to transmit the signal to the processor. 
 
     
     
       21. The method of  claim 20 , wherein, in the generating, directing, detecting, measuring, and determining steps:
 the integral apparatus comprises:
 a wrist watch further comprising an invasive glucose sensor configured to use blood or interstitial fluid to calibrate the noninvasive glucose sensor, or 
 a pair of glasses, wherein the feedback unit is a head up display associated with the glasses, or 
 
 the separated apparatus comprises a contact lens including the noninvasive glucose sensor. 
 
     
     
       22. The method of  claim 21 , wherein, in the generating, directing, detecting, measuring, and determining steps, the wrist watch further comprises of a pulse rate monitor, a blood oxygenation monitor, a body temperature monitor, and/or a blood pressure monitor. 
     
     
       23. The method of  claim 22 , further comprising:
 wirelessly communicating pulse rate, blood oxygenation, body temperature, and/or blood pressure with a cell phone, and 
 displaying a current glucose concentration and a graph of glucose concentration vs. time. 
 
     
     
       24. The method of  claim 23 , further comprising:
 wirelessly communicating with a health care facility or a non-health care facility.